VCOM Carolinas Research Day 2023

Clinical Studies

Significant Hypophosphatemia is Predictive of Brain Death in Severe Traumatic Brain Injury Lana E. Maniakhina BS, Sean M. Muir BS, Nichole Tackett BS, Daniel Johnson DO, Caleb J. Mentzer DO, Michael G. Mount DO Spartanburg Regional Healthcare System, Division of Surgery, Spartanburg, SC Edward Via College of Osteopathic Medicine, Spartanburg, SC Abstract Results Conclusions

Abstract #CLIN-3

Importance of Phosphate • Significant role in multiple intracellular pathways.

Mean Lowest Recorded Phosphate Level (LRPL) • 57 patients with confirmatory brain death (BD), LRPL was 1.67 ± 0.79 mEq/L (mean ± SD) • 279 non-brain death group (“no brain death”), LRPL was 2.16 ± 0.92 mEq/L (mean ± SD) • Statistical significance p< 0.00004 (Table 1) Analysis and Results • Univariate analysis demonstrated hypophosphatemia (HP) was correlated with BD (p<0.002) • Multivariate analysis showed HP was only correlation with a p value <0.0001, while no other measured physiologic or metabolic derangements demonstrated significant correlation with progression to BD • Statistical analysis determined the LRPL was statistically significant in patients who were confirmed BD compared to those that were not confirmed BD (p-value <0.0004*) • Results showed fewer days on ventilator and shorter ICU stay for patients with confirmed BD, which is attributed to higher mortality rate. BD had mortality rate of 100%, whereas non-BD mortality was 25%

Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality worldwide. 1 Severe TBI carries the greatest risk of brain death progression. 2 There are currently no laboratory markers that predict patient’s outcome. 3 We hypothesize that the degree of hypophosphatemia (HP) in TBI is an indicator for progression to brain death. A total of 336 patients, ages 15-89, with GCS of 8 or less at admission were identified and retrospectively analyzed. Demographics, laboratory studies, and brain-death (BD) were collected. Univariate analysis demonstrated HP was correlated with BD (p<0.0002). Multivariate analysis showed that phosphate was the only measured electrolyte correlated to BD with a p value<0.0001. Mechanism of hypophosphatemia may be related to BD progression and provide future areas for study.

References • Sufficient phosphate levels are important for mitigating secondary brain insults, preserving cerebral perfusion, and optimizing cerebral energy consumption • No definitive answers have been found to explain etiology behind HP. Theories include ventilator-induces hypocapnia with subsequent rise in pH and intracellular shift of phosphate, secondary aldosteronism, mannitol administration, excessive catecholamine and cytokine surge, and increased requirements for phosphate-containing intermediate metabolites of energy metabolism Severe Traumatic Brain Injury (sTBI) and Progression to Brain Death (BD) • Significant HP is associated with progression to BD. • Patients with sTBI demonstrate complex derangement in physiology leading to cytokine storm and biochemical imbalances such as HP that can interfere with neuromuscular exam • Currently, time required to correct significant electrolyte imbalances can potentially delay diagnosis of BD. Early and aggressive correction is recommended • Future work will look towards elucidating role of HP as predictive of BD in sTBI 1.GBD 2016. Traumatic Brain Injury and Spinal Cord Injury Collaborators (2019). Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. Neurology , 18 (1), 56 – 87. https://doi.org/10.1016/S1474-4422(18)30415-0 2.Marehbian, J., Muehlschlegel, S., Edlow, B.L. et al. (2017). Medical management of the severe traumatic brain injury patient. Neurocrit Care 27, 430 – 446. https://doi.org/10.1007/s12028-017-0408-5 3.Murray GD, Brennan PM, Teasdale GM (2018). Simplifying the use of prognostic information in traumatic brain injury. Part 2: Graphical presentation of probabilities. J Neurosurg. 128(6):1621-1634. doi: 10.3171/2017.12. JNS172782. We would like to thank Angela Wilson for her assistance with statistical analysis. The IRB at Spartanburg Regional Heatlhcare system approved the project on 5/27/2022. The IRBnetID: 1885528-2. Acknowledgements

Methods

Retrospective study • Conducted at Spartanburg Regional Health System (SRHS) Spartanburg medical center (SMC) – Church Street campus, Spartanburg, South Carolina • Total of 425 patients, ages 15-89, with GCS of 8 or less admitted to the ICU between 1/1/2018 and 12/31/2021 • 89 patients were excluded secondary to incomplete data in the charts; therefore, data analysis was performed on 336 patients Data Collection and Analysis • Demographics, GCS on admission, lowest recorded phosphate, highest sodium, lowest sodium, highest potassium, lowest potassium, lowest magnesium, total ICU days, and total days on ventilator • Continuous variables compared using unpaired T test assuming unequal variance • Chi Square Test used to analyze categorical variables. • Univariate and multivariate analyses were performed using JMP software • A p- value of 0.05 was deemed statistically significant

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